We seek to understand the differences between inflammatory breast cancer that arises in an area of surprisingly high proportion (Egypt) and in the U.S. where the proportion is 5 times lower. Egypt offers a unique setting for the comparative study of inflammatory breast cancer because: 1) Egypt has high proportion of IBC (10% of all breast cancers versus approximately 2-4% in the U.S.; 2) Extensive environmental exposures and documented high levels of markers of environmental exposures in breast cancer patients in Egypt; 3) Younger age of onset of both breast cancer in general and of IBC; 4) Our published research that showed clearly distinct molecular pathways in Egyptian colon tumors from the welldefined pathways of tumors of Western patients; and 5) Our recent research that showed alterations in two genes in 90 percent of IBC tumors: RhoC guanosine triphosphatase over-expression and WNT-1 induced secreted protein 3 (WISPS) as potential markers of IBC in the US. Our specific aims are: (1) To define the unique molecular genetic profile of IBC tumors from Egypt and to compare it with the profile of IBC tumors from the U.S., (2) to explore if specific molecular changes, such as, RhoC, p53, and Her-2/neu overexpression or loss of WISPS can predict phenotypic characteristics, such as age of disease-onset, rate of tumor progression, and family history of IBC in patients from Egypt and the U.S., and (3) to identify environmental or lifestyle-related factors that correlate with IBC profile in tumors from Egypt. We now propose to explore the epidemiologic and molecular profile of 100 IBC patients from Egypt and to compare them with 100 IBC patients from the U.S. We will compare the frequency of these molecular characteristics in IBC tumors from Egyptian versus U.S. IBC tumors. In addition, we will perform exploratory studies of cDNA expression profile 10 tumors from each geographic group, matched for severity of clinical symptoms at presentation and age, to expand our potential list of differentially expressed genes, besides those candidates derived from those derived from our previous work and that of others. With the large number of patients included in this study from Egypt and the U.S., we may be able develop a better idea about molecular pathways and prognostic factors in IBC pathogenesis.